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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KCNH4
potassium voltage-gated channel subfamily H member 4
Chromosome 17 · 17q21.2
NCBI Gene: 23415Ensembl: ENSG00000089558.9HGNC: HGNC:6253UniProt: Q9UQ05
11PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
potassium ion transmembrane transportplasma membraneregulation of membrane potentialvoltage-gated potassium channel activitymultiple sclerosisMyasthenia gravisLambert-Eaton myasthenic syndromeMuscle weakness
✦AI Summary

KCNH4 encodes a pore-forming alpha subunit of voltage-gated delayed rectifier potassium channels that activates at hyperpolarized potentials and exhibits slow deactivation kinetics without inactivation 1. The channel is primarily expressed in the nervous system, with substantial overlap with other Elk family members KCNH3 and KCNH8 1. KCNH4 can form heteromultimers with other Elk subfamily channels but not with Eag, Erg, or Kv family channels 1. Beyond neuronal function, KCNH4 appears involved in cellular proliferation control, as tau protein overexpression significantly reduces KCNH4 mRNA levels in neuroblastoma cells, correlating with enhanced cell proliferation rates 23. Disease relevance includes potential contributions to intellectual disability when duplicated in 17q21.2 chr17 aberrations 4, and involvement in metabolic regulation through membrane transport mechanisms affecting milk lactose content in dairy cattle 5. Additionally, KCNH4 is implicated in feline hypokalemia as a candidate gene near WNK4 mutations 6, and its downregulation occurs in CLN1 disease cellular models, potentially contributing to altered neuronal excitability underlying epileptic phenotypes 7. These findings suggest KCNH4 functions in both neuronal excitability regulation and broader cellular metabolic processes.

Sources cited
1
KCNH4 forms voltage-gated delayed rectifier K+ channels with hyperpolarized activation and can form heteromultimers with Elk family channels
PMID: 12890647
2
Tau overexpression reduces KCNH4 mRNA levels in neuroblastoma cells and enhances proliferation
PMID: 26576773
3
Tau transfection downregulates KCNH4 mRNA and improves N2A cell proliferation
PMID: 25590133
4
KCNH4 duplication in 17q21.2 may contribute to intellectual deficiency
PMID: 23337768
5
KCNH4 is associated with milk lactose regulation through membrane transport mechanisms
PMID: 29246110
6
KCNH4 is a candidate gene for feline hypokalemia near WNK4 mutations
PMID: 23285264
7
KCNH4 downregulation occurs in CLN1 disease models, potentially affecting neuronal excitability
PMID: 33390903
Disease Associationsⓘ20
multiple sclerosisOpen Targets
0.59Moderate
Myasthenia gravisOpen Targets
0.56Moderate
Lambert-Eaton myasthenic syndromeOpen Targets
0.55Moderate
Muscle weaknessOpen Targets
0.46Moderate
congenital myasthenic syndromeOpen Targets
0.43Moderate
Congenital myasthenic syndromesOpen Targets
0.43Moderate
autoimmune diseaseOpen Targets
0.37Weak
neoplasmOpen Targets
0.37Weak
autoimmune disorder of the nervous systemOpen Targets
0.37Weak
cancerOpen Targets
0.37Weak
cardiac arrhythmiaOpen Targets
0.37Weak
immune system diseaseOpen Targets
0.37Weak
Increased muscle fatiguabilityOpen Targets
0.37Weak
nervous system diseaseOpen Targets
0.37Weak
nervous system neoplasmOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
neuromuscular diseaseOpen Targets
0.37Weak
neuromuscular junction diseaseOpen Targets
0.37Weak
paraneoplastic neurologic syndromeOpen Targets
0.37Weak
small cell carcinomaOpen Targets
0.37Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
AMIFAMPRIDINEApproved
Voltage-gated potassium channel blocker
Myasthenia gravis
AMIFAMPRIDINE PHOSPHATEApproved
Voltage-gated potassium channel blocker
Lambert-Eaton myasthenic syndrome
DALFAMPRIDINEApproved
Voltage-gated potassium channel blocker
multiple sclerosis
GUANIDINEPhase III
Voltage-gated potassium channel blocker
neuroendocrine neoplasm
GUANIDINE HYDROCHLORIDEApproved
Voltage-gated potassium channel blocker
Myasthenia gravis
NERISPIRDINEPhase II
Voltage-gated potassium channel blocker
multiple sclerosis
TEDISAMILApproved
Voltage-gated potassium channel blocker
cardiac arrhythmia
Related Genes
KCNH8Shared pathway100%KCNH7Shared pathway100%KCNH3Shared pathway100%KCNH5Shared pathway80%KCNU1Shared pathway75%KCNQ5Shared pathway75%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
98%
Heart
24%
Lung
12%
Ovary
11%
Liver
7%
Gene Interaction Network
Click a node to explore
KCNH4KCNH8KCNH7KCNH3KCNH5KCNU1KCNQ5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UQ05
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.50Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.37 [0.28–0.50]
RankingsWhere KCNH4 stands among ~20K protein-coding genes
  • #16,789of 20,598
    Most Researched11
  • #349of 1,025
    FDA-Approved Drug Targets5
  • #3,002of 17,882
    Most Constrained (LOEUF)0.50 · top quartile
Genes detectedKCNH4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content.
PMID: 29246110
BMC Genomics · 2017
1.00
2
A de novo 17q21.2 duplication in a boy with developmental delay and dysmorphic features.
PMID: 23337768
Eur J Med Genet · 2013
0.90
3
The Tau-Induced Reduction of mRNA Levels of Kv Channels in Human Neuroblastoma SK-N-SH Cells.
PMID: 26576773
J Mol Neurosci · 2016
0.80
4
Lung cancer vaccines and gene therapy.
PMID: 12867069
Lung Cancer · 2003
0.70
5
Distribution and functional properties of human KCNH8 (Elk1) potassium channels.
PMID: 12890647
Am J Physiol Cell Physiol · 2003
0.60